Posted by Friends of FSH Research on Feb 27, 2019
Update by Sachiko Homma, PhD
See grant Mechanisms of DUX4-induced muscle atrophy
The ubiquitin-proteasome system (UPS) is responsible for degrading 80-90% of proteins including many regulated, short-lived, abnormal, denatured, or, in general, damaged proteins. The UPS has been shown to play an important role in mediating muscle atrophy. DUX4 expression in myogenic cells has been demonstrated to change expression of many genes those are involved in the UPS. Despite the obvious importance of this pathway in FSHD pathology, to our knowledge, no other lab is studying proteasome regulation in FSHD muscle. Therefore, the purpose of this project is to identify the roles of this pathway in DUX4-induced muscle atrophy. During this funding period, I initiated and established a collaboration with Dr. Goldberg (Harvard Medical School), that made it possible for me to assay and study mechanisms and regulation of this pathway in more detail. Our preliminary results showed DUX4 expression enhanced proteasome activity in myogenic cell culture and muscle tissues from FSHD mouse model (FLexDUX4, kind gift from Dr. Jones) and subset of FSHD patients (a kind gift from Telethon Italy and the Myobank-AFM). We are going to examine the mechanisms how DUX4 activates proteasome function and if this pathway can be a therapeutic target for FSHD.